Prothrombin complex concentrates in warfarin anticoagulation reversal

Anticoagulation is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. The annual incidence of major bleeding in trials and cohort studies has been reported to be between 1.1% and 2.3% in patients treated with warfarin to achieve an international normalized ratio (INR) of 2.0 to 3.0. These rates are derived from carefully controlled studies, but in “unselected” outpatients, the risk of bleeding was found to be as high as 4.3% in patients receiving warfarin(1). For minor bleeding due to Vitamin K antagonists (VKA), discontinuation of anticoagulation therapy (with or without the administration of vitamin K) is sufficient to bring bleeding under control. However, for patients with major bleeding during VKA use, rapid reversal of anticoagulation is desirable, particularly if bleeding is life threatening or an urgent surgical procedure is required. Two products are suitable for increasing the concentration of vitamin K-dependent coagulation factors in these situations: fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC)(2). Both products contain coagulation factors II, VII, IX and X, which are down-regulated during VKA therapy. PCC present several advantages over FFP, the most significant being the potential to completely reverse warfarin-induced anticoagulation in minutes, as compared with the longer periods required for the issuing of FFP from blood banks, the requirement of pre-transfusion tests, thawing and transfusion. Additional disadvantages of FFP include potential allergic reactions, transfusion-related acute lung injury (TRALI), volume overload and transfusiontransmitted diseases. For these reasons, some guidelines suggest a preferential use of PCC over FFP for warfarin reversal(3). Although all PCC contain factors II, IX and X, there is significant variability in the factor VII content. It has been argued by some that PCC with little factor VII (the so called 3-factor PCC) produce poorer correction of the INR and should not be used for warfarin reversal(3,4). The aim of the present study was to review the scientific literature on employing PCC for warfarin reversal.